The broad objective of this research is to understand the mechanisms of differentiation of vertebrate hard tissues, including bone, teeth and abnormally calcified tissues. We are investigating four principal aspects of skeletogenesis and dentinogenesis: (1) activation of fibroblasts, osteoblasts, odontoblasts and ameloblasts to undergo differentiation: (2) secretory activity of these cells and polymerization of the organic matrix surrounding them; (3) nucleation and growth of the hydroxyapatite crystals in the mineralizing matrix; and (4) resorption of crystallites during regression and remodelling of hard tissue. The fine structure of differentiating enamel in representative sharks and teleost fishes is being investigated. Fibrillogenesis of giant collagenous fibers (ceratotrichia) in shark fins is being compared with fibrillogenesis of homologous fiber (actinotrichia) in fins of teleost. Agents known to affect fibrillogenesis or mineralization are being used to modify early differentiation or regeneration of fish fins and frog tadpole limbs. These agents include B-aminopropionitrile, gamma radiation, thyroxine, parathormone, thyrocalcitonin, prolactin, cortisone, actinomycin D, chloramphenicol and malathion. Regression of bone is being studied in regenerating fish fins.